Alcohol Dependence, Smoking, Tobacco Dependence
Conditions
Keywords
smoking, tobacco dependence, alcohol dependence
Brief summary
Alcohol dependence is a significant and prevalent public health problem affecting approximately 4% of the U.S. adult population. Individuals with alcohol dependence actively seek treatment annually, and long-term alcohol abstinence varies from 40-60%. Because of the high smoking prevalence and trends toward heavier smoking, alcoholic smokers are at high risk for both morbidity and mortality related to alcohol consumption and tobacco dependence. Although several studies have evaluated pharmacotherapy for tobacco dependence in recovering alcoholic smokers, few have evaluated pharmacotherapy for tobacco dependence among currently drinking alcoholic smokers. Varenicline is the most effective medication currently available for treating tobacco dependence. While some randomized trials have included recovering alcoholics, active alcoholism has been an exclusion criteria for these trials. Thus, this proposal would be the first such clinical trial in currently drinking alcoholic smokers. In addition to helping smokers to stop smoking, varenicline has also been shown to reduce alcohol consumption in rats. The goal of this proposal is to explore the potential efficacy of varenicline for treating tobacco dependence and reducing drinking among alcohol dependent smokers. The investigators hypothesize that 12 weeks of treatment with varenicline, a partial nicotinic acetylcholine receptor agonist will be more effective than placebo in treating tobacco dependence and reducing nicotine withdrawal symptoms in currently drinking alcoholic smokers. The investigators will also explore whether varenicline has an effect on drinking behavior among currently drinking alcoholics. The investigators propose the following specific aims to test these hypotheses in 70 currently drinking alcoholic smokers recruited at the Mayo Clinic in Rochester, Minnesota.
Detailed description
Seventy smokers who are currently alcohol dependent will be enrolled to this study. If found to be study eligible they will be randomized to either active varenicline or placebo for 12 weeks. During these two weeks, they will be seen either weekly or biweekly. At the end of treatment, they will be followed up for an addition 12 weeks. Their last study visit will be 6 months after randomization.
Interventions
DRUGVarenicline
varenicline 1.0 mg dose, twice daily for 12 weeks
DRUGplacebo
sugar pill twice daily for 12 weeks
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Male or non-pregnant female cigarette smokers 18-years-of-age or older and reporting smoking at least an average of 10 cigarettes per day for the past year; 2. Subject is alcohol dependence based on DSM IV criteria as assessed by the Mini-International Neuropsychiatric Interview (MINI) and the physician investigator;3 3. Subject is currently drinking alcoholic beverages as assessed by the physician investigator; 4. Subject is a female subject of non-childbearing potential or a female subject of childbearing potential - who is using contraceptives and has a negative pregnancy test result; 5. Subject must be able to complete all the study visits; 6. Subject has the ability to participate fully in all aspects of the study and keep scheduled appointments; 7. Subject must be in good general health as determined by medical history, physical exam and physician investigator; 8. Subject must provide written informed consent to participate in the study;
Exclusion criteria
1. Subject is a female who is pregnant, lactating or likely to become pregnant during the trial and not willing to use an acceptable form of contraception during the medication phase, (for women of child-bearing potential, a pregnancy test will be performed prior to entry into the study and at the end of the medication phase); 2. Subject has another household member in study; 3. Known allergy to varenicline; 4. Subject is currently (in previous 30 days) using other behavioral or pharmacologic tobacco cessation program (i.e., behavioral therapy, nicotine replacement therapy, clonidine, varenicline, bupropion SR, nortriptyline or doxepin) and unwilling or unable to discontinue use; 5. Subject has an unstable medical condition as determined by the physician investigator; 6. Subject describes having a medical history of: a) unstable angina; b) myocardial infarction within the past 3 months; c) coronary angioplasty or d) an untreated cardiac dysrhythmia; 7. Subject has a personal history of renal failure or is on renal dialysis; 8. Subject has a current moderate or severe depression as assessed by the Center for Epidemiologic Studies-Depression survey (CES-D) and physician investigator; 9. Subject has, as defined by the Columbia Suicide Severity Rating Scale (C-SSRS) current non-specific suicidal thoughts, or have a lifetime history of a suicidal attempt (defined as potentially self-injurious act committed with at least some wish to die, as a result of act); 10. Subject has current (past 30 days) major depressive disorder or has a history of another psychiatric disorder such as psychosis or bipolar disorder; 11. Subject currently uses of other tobacco products (i.e. pipe, cigar, smokeless tobacco) within the past 30 days; 12. Subject currently has cancer \[excluding non melanoma skin cancer\] not in remission (cancer free for 5 years or more); 13. Subject currently has Type 1 diabetes; 14. Subject has untreated hypertension or baseline systolic blood pressure \> 180 or diastolic \> 100; 15. Subject is currently on treatment with another investigational drug (within 30 days of study entry);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prolonged Smoking Abstinence at End of 12 Weeks of Varenicline Treatment | 12 weeks | Prolonged smoking abstinence will be identified by a negative response to the question, Since 2 weeks after your TQD, have you smoked any tobacco, even a puff, for 7 consecutive days or at least once each week on 2 consecutive weeks? |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prolonged Abstinence at 24 Weeks | week 24 | Prolonged abstinence is identified by a negative response to the question, Since 2 weeks after your TQD, have you smoked any tobacco, even a puff, for 7 consecutive days or at least once each week on 2 consecutive weeks? |
| Heavy Drinking Days at End of Treatment | week 12 | Heavy drinking is defined as 5 standard alcohol drinks or greater for men and 4 standard alcohol drinks or greater for women. The number of heavy drinking days per month was determined using the timeline follow-back method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline varenicline 1.0 mg twice daily for 12 weeks
Varenicline: varenicline 1.0 mg dose, twice daily for 12 weeks | 16 |
| Sugar Pill Varenicline look alike sugar pill twice daily for 12 weeks
placebo: sugar pill twice daily for 12 weeks | 17 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Withdrawal by Subject | 1 | 7 |
Baseline characteristics
| Characteristic | Varenicline | Sugar Pill | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 17 Participants | 33 Participants |
| Age, Continuous | 40.2 years STANDARD_DEVIATION 11.9 | 38.8 years STANDARD_DEVIATION 10.4 | 39.5 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 17 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 16 Participants | 30 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 21 Participants |
| tobacco use | 19.1 cigarettes per day STANDARD_DEVIATION 7.5 | 21.6 cigarettes per day STANDARD_DEVIATION 7.3 | 20.4 cigarettes per day STANDARD_DEVIATION 7.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 16 | 2 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 |
Outcome results
Primary
Prolonged Smoking Abstinence at End of 12 Weeks of Varenicline Treatment
Prolonged smoking abstinence will be identified by a negative response to the question, Since 2 weeks after your TQD, have you smoked any tobacco, even a puff, for 7 consecutive days or at least once each week on 2 consecutive weeks?
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Prolonged Smoking Abstinence at End of 12 Weeks of Varenicline Treatment | 6 participants |
| Sugar Pil | Prolonged Smoking Abstinence at End of 12 Weeks of Varenicline Treatment | 1 participants |
p-value: 0.034Fisher Exact
Secondary
Heavy Drinking Days at End of Treatment
Heavy drinking is defined as 5 standard alcohol drinks or greater for men and 4 standard alcohol drinks or greater for women. The number of heavy drinking days per month was determined using the timeline follow-back method.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Heavy Drinking Days at End of Treatment | 7.9 days | Standard Deviation 8.3 |
| Sugar Pil | Heavy Drinking Days at End of Treatment | 9.1 days | Standard Deviation 7.2 |
90% CI: [-4.7, 2.1]
Secondary
Prolonged Abstinence at 24 Weeks
Prolonged abstinence is identified by a negative response to the question, Since 2 weeks after your TQD, have you smoked any tobacco, even a puff, for 7 consecutive days or at least once each week on 2 consecutive weeks?
Time frame: week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Prolonged Abstinence at 24 Weeks | 4 participants |
| Sugar Pil | Prolonged Abstinence at 24 Weeks | 0 participants |
p-value: 0.044Fisher Exact